XMRV Replication Studies

I looked up some of the molecular biology re retroviruses.The reverse transcriptase of a retovius has no proofreading ability leading to considerable variation in the dna sequences of the inserted genome.In short the viruses drift all over the place and produce antigenic shifts similar to the flu virus this with a slow replication rate ,fast degredation in sera make xmrv one difficult bug to detect unless you target the specific deletion sequence in the env gene -this is the only way fto know for sure(if such a thing really exists) that its there and you dont have an endogenous virus this bug is a doozy -on the face of it relatively simple but with real twits in its replication process-----if you dont really understand this virus--designing a study to find it is really tricky-It doesn,t behave like Viruses of this type are supposed to----how it got detected in the first place amazes me----If anything can be tagged as a stealth virus this is it!.

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My understanding is that this is the reason the pol gene is often used for detection in retroviral research. However WPI did not use pol and claims there is very little mutation of XMRV. So therefore they used gag and in one replication they used env. So I'm not sure how your comments connect to this specific XMRV finding...if XMRV is slow mutation. Also, the problems with degredation are apparently manageable as positives are being found by VIP Dx with samples shipped overnight.

I,ve always thought that ME should be called mitochondrial encephalopathy-----the symptoms of MLAS, a known mitochondrial disorde,r and ME/CFS are virtually the same, virus gets in --immune system activated hpa axis down mitochondrial damage immune system permanently swiched on hpa axis stays down complete autonomic deregulation encephalopathy-------it certainly explains the whole range of symptoms

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That is an interesting name idea. MELAS does not sound like CFS, since it is actual dementia and not just brain fog. But one thing is for certain, CFS is not a 'syndrome', I would call it some type of spectrum disorder. ME fits in the spectrum along with probably a dozen other conditions.

I,ve always thought that ME should be called mitochondrial encephalopathy-----the symptoms of MLAS, a known mitochondrial disorde,r and ME/CFS are virtually the same, virus gets in --immune system activated hpa axis down mitochondrial damage immune system permanently swiched on hpa axis stays down complete autonomic deregulation encephalopathy-------it certainly explains the whole range of symptoms

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The CFIDS Association is funding Dr. Shungu, I think it is, who has found evidence of mitochondrial problems in the brain. Who knows?

there is a spectrum of severity of symptoms with melas although progressive dependent on degree of mitochondrial damage-----mitochondrial damage cuses problems with B12 levels and can obviously eventually lead to dementia
this produces a type of encephalopathy called Korsokoffs syndrome---spelling might be dodgy here!

mitochondrial damage has been linked to the symptoms of cfs(i hate that name) the worse the damage the more severe the symptoms Myhill et al'

If the virus uses reverse transcriptase it will produce base sequence changes quite ofter depending as you say on its replication rate The Pol gene will detect a retrovirus------but the older the sample---the more chance of mutation

At least some of the negative studies used relatively old samples of indeterminate age-----There is only one gene sequence unique to XMRV(or lack of!----At least according to the books------I think I saw a piece from the WPI claiming that other countries might have different strains of the virus I,d be suprised if that wasn,t true

There is calcium channelopathy in ME from what I remember, if so there most likely will be at least some level of downstream mitochondrial dsyfunction. Up to now everything found in autism more or less parallels ME findings, and the other way around (apart from Rnase L pathways, which have not been looked at in autism yet) Look up http://autismcalciumchannelopathy.com/Mitochondrial.html - one of the latest papers is not referenced but more or less confirms the previous ones. Pathology one most interesting.

Mito dysfunction is found in HIV infection, again as downstream of vgcc overactivation and mito calcium overload being at least one mechanism...

On a slightly different note interesting that HIV directly affects ryanodine channels, which are not only linked and engage in crosstalk with mitochondria, but are being investigated for involvement in ME/CFS for their involvement in fatigue.

“The findings described here provide the first evidence that postviral fatigue syndrome may be due to a mitochondrial disorder precipitated by a virus infection…Evidence of mitochondrial abnormalities was present in 80% of the cases with the commonest change (seen in 70%) being branching and fusion of cristae, producing ‘compartmentalisation’. Mitochondrial pleomorphism, size variation and occasional focal vacuolation were detectable in 64%…Vacuolation of mitochondria was frequent…In some cases there was swelling of the whole mitochondrion with rupture of the outer membranes…prominent secondary lysosomes were common in some of the worst affected cases…The pleomorphism of the mitochondria in the patients’ muscle biopsies was in clear contrast to the findings in normal control biopsies…Diffuse or focal atrophy of type II fibres has been reported, and this does indicate muscle damage and not just muscle disuse” (WMH Behan et al. Acta Neuropathologica 1991:83:61-65).

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Mitochondrial problems have always seemed to explain all my symptoms. If the batteries are dead nothing works. I think it is acquired rather than genetic which is why we don't have MELAS but acquired mitochondrial encephalopathy is an accurate description.

My understanding is that this is the reason the pol gene is often used for detection in retroviral research. However WPI did not use pol and claims there is very little mutation of XMRV. So therefore they used gag and in one replication they used env. So I'm not sure how your comments connect to this specific XMRV finding...if XMRV is slow mutation. Also, the problems with degredation are apparently manageable as positives are being found by VIP Dx with samples shipped overnight.

That is an interesting name idea. MELAS does not sound like CFS, since it is actual dementia and not just brain fog. But one thing is for certain, CFS is not a 'syndrome', I would call it some type of spectrum disorder. ME fits in the spectrum along with probably a dozen other conditions.

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I suffered alexia,agnosia,agraphia,dyscalcula, frontal lobe psychic dyscognitive siesures, aura continua and a host of other symptoms which rendered me a cognitive cripple for two years.This was coupled with complete autonomic dysregulation and hyperimmune activity.This is, as you know, like having chronic severe flu and lasted for about two years prior to my cognitive collapse I could not push a hoover or even cross a room-Brain fog doesn't even come close! The only other known cause of this group of symptoms is mitochondrial dysfunction.I.m not saying that this is a definate cause of all ME cases but would fit my experience and my level of mitochondrial function.If XMRV can integrate into eukaryotic DNA then it should also be able to integrate into the prokayotic DNA of the mitochondria.Other retroviruses can so why not XMRV?----I do however agree with the idea that cfs (Ugh!) has many causes Ive, got the mutation rate figures somewhere i,ll try to dig them up

Keywordschronic fatigue syndrome; ion channels; neuronal instability; migraine; epilepsy; depressionAbstractMany symptoms of chronic fatigue syndrome (CFS), including severity of fatigue, may be periodic, fluctuant and induced by physical and mental activities, including trauma and stress. The fatigue in CFS is distinct from the fatigue of neuromuscular disorders but is similar to that found in disorders of the central nervous system such as multiple sclerosis, Parkinson's disease and multiple system atrophy. Though fatigue is a common symptom of depressive disorders, it is now clear that CFS patients differ from patients with major depression in their symptoms, biologic markers such as steroid metabolism and response to standard antidepressant drug therapy. In this paper, we propose dysfunctional ion channels in the cell membranes as the key abnormality in CFS which may also be responsible for the altered neuroendocrine functions reported in this condition. In our hypothesis, changes in the neuronal ion channel function from time to time offers a rational basis to explain fluctuating fatigue and related symptoms in CFS. Finally, ion channel abnormality leading to selective neuronal instability may be the common disease mechanism in CFS and other paroxysmal disorders affecting brain functions such as migraine and epilepsy. Copyright 1999 John Wiley & Sons, Ltd.

I also saw your post where you said that senior members of the forum could post to the library. I don't always trust myself to pick articles that are relavant/not offensive/whatever. If we post a paper that is inappropriate will someone be monitoring and take it off?

How would you go about testing for mitochondrial abnormalities?
Is there a test commercially available?

Rachel xx

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Hi Rachel,

I see that you are in London, so you are in luck. There's a lab to the southwest of you--I think it's called Acumen. Dr. Sarah Myhill did a study on cfs and mitochondria. Can't remember the details. I don't think we have a lab in the U.S. that does these good tests. When I get a minute I'll get you more accurate information, unless someone else jumps in.

I also saw your post where you said that senior members of the forum could post to the library. I don't always trust myself to pick articles that are relavant/not offensive/whatever. If we post a paper that is inappropriate will someone be monitoring and take it off?

Thanks,

Maxine

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Oh, Maxine...go ahead and post any papers in the Library that you think might be interesting to us. I TRUST YOU :Sign giggle:

I guess you weren't around on Saturday when I loaded up the new Library with 27 studies and took over the [New Posts] queue. Got a few PMs asking me why I was reposting articles that we've already discussed.

I guess you weren't around on Saturday when I loaded up the new Library with 27 studies and took over the [New Posts] queue. Got a few PMs asking me why I was reposting articles that we've already discussed.

I guess you weren't around on Saturday when I loaded up the new Library with 27 studies and took over the [New Posts] queue. Got a few PMs asking me why I was reposting articles that we've already discussed.

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I'll admit that I thought, "Ho hum." I thought the library would be one of those disorderly, hard-to-navigate mish-mashes that are often connected to Yahoo groups. But when I visited... Wow! It's great. A really good easy-to-use resource.